A Pre-mRNA–Associating Factor Links Endogenous siRNAs to Chromatin Regulation

Laboratory of Genetics, University of Wisconsin Madison, Madison, Wisconsin, United States of America.
PLoS Genetics (Impact Factor: 7.53). 08/2011; 7(8):e1002249. DOI: 10.1371/journal.pgen.1002249
Source: PubMed


In plants and fungi, small RNAs silence gene expression in the nucleus by establishing repressive chromatin states. The role of endogenous small RNAs in metazoan nuclei is largely unknown. Here we show that endogenous small interfering RNAs (endo-siRNAs) direct Histone H3 Lysine 9 methylation (H3K9me) in Caenorhabditis elegans. In addition, we report the identification and characterization of nuclear RNAi defective (nrde)-1 and nrde-4. Endo-siRNA-driven H3K9me requires the nuclear RNAi pathway including the Argonaute (Ago) NRDE-3, the conserved nuclear RNAi factor NRDE-2, as well as NRDE-1 and NRDE-4. Small RNAs direct NRDE-1 to associate with the pre-mRNA and chromatin of genes, which have been targeted by RNAi. NRDE-3 and NRDE-2 are required for the association of NRDE-1 with pre-mRNA and chromatin. NRDE-4 is required for NRDE-1/chromatin association, but not NRDE-1/pre-mRNA association. These data establish that NRDE-1 is a novel pre-mRNA and chromatin-associating factor that links small RNAs to H3K9 methylation. In addition, these results demonstrate that endo-siRNAs direct chromatin modifications via the Nrde pathway in C. elegans.

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    • "siRNAs are 21–22 nucleotides in length and are produced from endogenous double stranded RNA. These molecules associate with Argonaute proteins that induce localized chromatin remodelling (Fagegaltier et al., 2009; Burkhart et al., 2011) and may maintain genes in a " poised " state, ready to be activated (Cernilogar et al., 2011). piRNAs are larger (23–29 nucleotides) and are produced by a different mechanism to siRNAs (reviewed in Castel and Martienssen, 2013). "
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    • "NRDE-4 functions downstream of the NRDE-1/2/3 interaction with nuclear mRNA target and is not required for this process [39]. NRDE-4 binds to chromatin and mediates recruitment of NRDE-1 to the target locus [39]. The compelling molecular characterization of the NRDE pathway sheds light on the first step in RNAiinduced TGS. "
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